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Meeting ReportOncology-Basic: Basic Science

PET imaging of tumor CXCR4 expression with 18F-T140

Orit Jacobson, Ido Weiss, Joshua Farber and Xiaoyuan Chen
Journal of Nuclear Medicine May 2010, 51 (supplement 2) 282;
Orit Jacobson
1Laboratory for Molecular Imaging and Nanomedicine, NIBIB/NIH, Bethesda, MD
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Ido Weiss
2Laboratory of Molecular Immunology, NIAID/NIH, Bethesda, MD
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Joshua Farber
2Laboratory of Molecular Immunology, NIAID/NIH, Bethesda, MD
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Xiaoyuan Chen
1Laboratory for Molecular Imaging and Nanomedicine, NIBIB/NIH, Bethesda, MD
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Abstract

282

Objectives Expression of the chemokine receptor CXCR4 by cancers has been shown to correlate with the aggressive biological behavior, including increased rates of cell proliferation and metastasis, and with decreased patient survival. However, fully optimized PET imaging agents for determining CXCR4 expression by tumor cells in vivo are not yet available. This study aims to develop a stable, F-18 labeled peptide that enables in vivo quantification of CXCR4 in cancer.

Methods TN-14003 (T140), a short peptide antagonist of CXCR4 with 1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl protecting groups on the ϵ-amino groups of the lysine residues was labeled with F-18 via N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) conjugation, followed by deprotection to afford 18F-T140 that is exclusively labeled on the alpha amine at the N-terminus. Blood stability tests, biodistribution, and PET imaging studies of 18F-T140 were carried out.

Results T140 was labeled with F-18 with a radiochemical yield of 10±2% based on 18F-SFB coupling. 18F-T140 was found to specifically bind to red blood cells (RBC) in vivo. The binding of 18F-T140 to RBCs was blocked with a small amount of unlabeled F-T140 which leads to better binding of 18F-T140 to CXCR4 positive tumors. PET studies demonstrated clear visualization of CXCR4 transfected but not control CXCR4 negative CHO tumors. Biodistribution experiments at 3 h post injection with the addition of minimal amount of F-T140 showed 3.11±0.1 %ID/g uptake in CXCR4 positive tumors, with tumor/blood ratio of 25.5±4.7 and tumor/muscle ratio of 21.8±0.6. Low amount of blocking agent also reduced whole body background.

Conclusions 18F-T140 can be used to determine tumor CXCR4 expression with additional advantages of low background and ready availability of F-18.

Research Support Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB)

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Journal of Nuclear Medicine
Vol. 51, Issue supplement 2
May 2010
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PET imaging of tumor CXCR4 expression with 18F-T140
Orit Jacobson, Ido Weiss, Joshua Farber, Xiaoyuan Chen
Journal of Nuclear Medicine May 2010, 51 (supplement 2) 282;

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PET imaging of tumor CXCR4 expression with 18F-T140
Orit Jacobson, Ido Weiss, Joshua Farber, Xiaoyuan Chen
Journal of Nuclear Medicine May 2010, 51 (supplement 2) 282;
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